SUMMARY: Iowa Superfund Research Program Overall The Iowa Superfund Research Program (ISRP) is a center of research excellence focused on polychlorinated biphenyls (PCBs). PCBs were widely produced in the mid-20th century and used in thousands of products, from common household items to construction materials, until the chemicals were banned 40 years ago. Today, people are still exposed to PCBs indoors and in communities surrounding Superfund sites. Recent ISRP research demonstrated that airborne PCBs present an especially urgent problem: Inhalation of airborne PCBs may be the most significant route for human exposure to these important toxic chemicals. The ISRP?s long- term goal is to develop recommendations to prevent and/or limit human exposure to airborne PCBs and to improve the health and well-being of the population. The ISRP renewal will focus on PCBs in air, particularly in buildings (especially schools) and those emitted from contaminated waters (including Superfund sites). We will examine the health impacts of inhaled PCBs, particularly on adolescents, with a focus on neurodevelopmental and metabolic effects. The ISRP will accomplish its long-term goal through the following integrated Specific Aims: 1) Clarify the biochemical mechanisms of toxicity of lower-chlorinated PCBs in adolescence. Two projects will address how PCBs and their metabolites are risk factors for altered neurodevelopment during adolescence and the mechanisms by which these compounds interfere with lipid metabolism. 2) Define susceptible populations, assess exposure and accumulation of these compounds (particularly in schools), and evaluate the relative importance of airborne vs. dietary exposure. Three cohorts of mothers and adolescents will help us evaluate individuals? exposure to airborne PCBs, the specific environments that contribute to inhalation exposure, and its importance compared to exposure through diet. 3) Reduce emissions of airborne PCBs from building materials, products, and contaminated sediments. We will investigate sources of airborne PCBs in indoor environments, determine the magnitude of emissions from contaminated waters, and identify cost-effective strategies to remove or reduce emissions. This includes development of a new approach using novel materials to sequester lower chlorinated PCBs in sediments and break down PCBs through microbial processes to reduce PCB emissions from contaminated waters. 4) Train and attract new scientists to the environmental health sciences. Our training program will enhance research skills in data science, chemical analysis, community engagement, and research translation. 5) Engage the scientific community and stakeholders in bi-directional communication on ISRP research priorities, findings, and recommendations. We will communicate the ISRP?s research approaches and findings to a wide range of researchers, agencies, and community stakeholders to maximize impact and enable communities to make timely, informed decisions to reduce local PCB exposure.